Editorial
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Nov 15, 2024; 15(11): 2167-2172
Published online Nov 15, 2024. doi: 10.4239/wjd.v15.i11.2167
Glucagon-like peptide-1 agonists: Role of the gut in hypoglycemia unawareness, and the rationale in type 1 diabetes
Hyder O Mirghani
Hyder O Mirghani, Internal Medicine, University of Tabuk, Tabuk 51941, Tabuk, Saudi Arabia
Author contributions: Mirghani HO conceived and designed the study, performed the literature search, drafting, critical revision, and provided final approval of the version to be published.
Conflict-of-interest statement: The author declared that there are no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hyder O Mirghani, MD, Professor, Internal Medicine, University of Tabuk, Prince Fahd Bin Sultan, Tabuk 51941, Tabuk, Saudi Arabia. s.hyder63@hotmail.com
Received: July 12, 2024
Revised: August 30, 2024
Accepted: September 5, 2024
Published online: November 15, 2024
Processing time: 95 Days and 21.5 Hours
Abstract

Type 1 diabetes is increasing and the majority of patients have poor glycemic control. Although advanced technology and nanoparticle use have greatly enhanced insulin delivery and glucose monitoring, weight gain and hypo-glycemia remain major challenges and a constant source of concern for patients with type 1 diabetes. Type 1 diabetes shares some pathophysiology with type 2 diabetes, and an overlap has been reported. The above observation created great interest in glucagon-like peptide-1 receptor agonists (GLP-1) as adjuvants for type 1 diabetes. Previous trials confirmed the positive influence of GLP-1 agonists on β cell function. However, hypoglycemia unawareness and dysregulated glucagon response have been previously reported in patients with recurrent hypoglycemia using GLP-1 agonists. Jin et al found that the source of glucagon dysregulation due to GLP-1 agonists resides in the gut. Plausible explanations could be gut nervous system dysregulation or gut microbiota disruption. This review evaluates the potential of GLP-1 agonists in managing type 1 diabetes, particularly focusing on their impact on glycemic control, weight management, and glucagon dysregulation. We provide a broader insight into the problem of type 1 diabetes mellitus management in the light of recent findings and provide future research directions.

Keywords: Glucagon-like peptide-1 receptor agonists; Glucagon response; Hypoglycemia unawareness; Gut; Type 1 diabetes

Core Tip: Poor glycemic control, nonadherence to insulin, vascular complications, and obesity remain major challenges in type 1 diabetes management. Glucagon-like peptide-1 receptor (GLP-1) agonists have been shown to address the above issues without significant hypoglycemia. The rationale for GLP-1 agonist use is based on the shared pathophysiology of type 1 and type 2 diabetes. The recent evidence of gut involvement in GLP-1 agonists induced hypoglycemia unawareness and glucagon dysregulation is of great concern and the emerging role of GLP-1 agonists in gut microbiota dysregulation and diversity could change diabetes management including type 1 diabetes. The use of GLP-1 agonists should be individualized.